Process for the manufacturing of iodinated contrast agents

Abstract

A process for the preparation of compounds of general formula (I) ##STR1## characterized in that the corresponding derivatives of general formula (II) ##STR2## are reacted with the compounds of general formula (III) ##STR3## wherein Z is halogen atom or a reactive residue of a sulfonic acid or a --N + (R 9 ) 3 cation wherein R 9 is a (C 1 -C 6 ) alkyl group and R 1 , R 2 , R 3 , R 4 , R 5 R 6 R 7 and R 8 are as herein defined.

We claim: 
     
       1. A process for the preparation of compounds of general formula (I) ##STR17## wherein R1, R2, R3, R4, which can be the same or different, are, independently, H or a linear or branched (C1-C10) alkyl group, optionally substituted by 1-6 hydroxy and/or alkoxy groups, or a polyoxaalkyl group comprising from 1 to 10 oxygen atoms and from 3 to 30 carbon atoms, or R1 and R2 or R3 and R4, taken together, form a (C2-C8) chain optionally interrupted by one or more N, O, S atoms, R5 is the group ##STR18## wherein R 6  and R 8  are H,   R7 is H or a (C1-C3) alkyl, hydroxyalkyl or alkoxyalkyl group, characterized in that the corresponding derivatives of general formula (II) ##STR19## wherein R1, R2, R3 and R4 are as previously defined and the hydroxy group on the benzene ring can be also present as salt of alkali metal or alkaline-earth metal or a (C2-C6) trialkylamine, are reacted with the compounds of general formula (III) ##STR20## wherein Z is halogen atom or a reactive residue of a sulfonic acid selected from the group consisting of methanesulfonyloxy, benzenesulfonyloxy and toluenesulfonyloxy or a --N+(R9)3 cation wherein R9 is a (C1-C6) alkyl group and     R6 R7 and R8 are as previously defined; and the reaction is carried out in a reaction solvent selected from the group consisting of protic solvents and dipolar aprotic solvents.     
     
     
       2. A process according to claim 1, wherein the compound of formula (II) is in the form of sodium salt. 
     
     
       3. A process according to claim 1, wherein the stoichiometric ratio of the compound of formula (III) and the compound of formula (II) is equal to 2. 
     
     
       4. A process according to claim 1, wherein the ether bond formation between the compounds of general formula (II) and the compounds of general formula (III) is carried out at a temperature comprised between room temperature and 120° C. 
     
     
       5. A process according to claim 1, wherein the reaction solvent is selected from the group consisting of: H2O, H2O/EtOH mixture, dimethylacetamide (DMA), methyl cellosolve and ethyl cellosolve.